Abstract
BackgroundMetabolic abnormalities that lead to type 2 diabetes mellitus begin in early childhood.ObjectivesWe investigate whether common genetic variants identified in adults have an effect on glucose in early life.Methods610 newborns, 463 mothers, and 366 fathers were included in the present study. Plasma glucose and anthropometric characteristics were collected at birth, 3, and 5 years. After quality assessment, 37 SNPs, which have demonstrated an association with fasting plasma glucose at the genome-wide threshold in adults, were studied. Quantitative trait disequilibrium tests and mixed-effects regressions were conducted to estimate an effect of the SNPs on glucose.ResultsRisk alleles for 6 loci increased glucose levels from birth to 5 years of age (ADCY5, ADRA2A, CDKAL1, CDKN2A/B, GRB10, and TCF7L2, 4.85x10-3 ≤ P ≤ 4.60x10-2). Together, these 6 SNPs increase glucose by 0.05 mmol/L for each risk allele in a genotype score (P = 6.33x10-5). None of the associations described in the present study have been reported previously in early childhood.ConclusionOur data support the notion that a subset of loci contributing to plasma glucose variation in adults has an effect at birth and in early life.
Highlights
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder resulting from the interplay of environmental, genetic, and epigenetic factors [1]
Our data support the notion that a subset of loci contributing to plasma glucose variation in adults has an effect at birth and in early life
Plasma glucose is maintained within a narrow physiological range by a balance between insulin secretion and action; glucose tolerance remains constant as long as a reduction in insulin sensitivity at target tissues is compensated by proportionate increases in insulin supply from pancreatic β-cells
Summary
Type 2 diabetes mellitus (T2DM) is a chronic metabolic disorder resulting from the interplay of environmental, genetic, and epigenetic factors [1]. Plasma glucose is maintained within a narrow physiological range by a balance between insulin secretion and action; glucose tolerance remains constant as long as a reduction in insulin sensitivity at target tissues is compensated by proportionate increases in insulin supply from pancreatic β-cells. Failure of this control mechanism results in dysglycemia and overt T2DM [3], which have an adverse impact on multiple organ systems. A meta-analysis of GWAS SNPs in 6,000 adolescents aged 9–16 years found 16 variants associated with FPG [16]. Metabolic abnormalities that lead to type 2 diabetes mellitus begin in early childhood.
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